Small cell-permeable natural products and their analogs play a crucial role in the treatment of disease. This proposal addresses the syntheses of several biologically active molecules relevant to the treatment of cancer, HIV, stroke and heart disease through "The Synthesis and Application of Chiral Cyclohexadienones." Optically enriched chiral cyclohexadienones are relatively inaccessible chemical entities. Their fragile nature coupled with the lack of enantioselective access has hampered their widespread synthetic applications. We intend to show that robust cyclohexadienones can be constructed to undergo a myriad of diastereoselective reactions including 1,2-, 1,4- and 1,6-additions, along with various rearrangements and cycloadditions. We intend to prove that these cyclohexadienones can be easily constructed in enantiopure form. We will establish the usefulness of these adducts as non-racemic cyclohexyl synthons through short syntheses to ascertain the subtleties of the surrounding synthetic chemistry. Each proposed synthesis addresses a target that is (or has proven to be) difficult to construct by current technologies and is highly relevant to national public health. It should become evident that the synthetic method proposed has eventual greater application in the assembly of future prospective drugs.